Manganese – lowers ammonia, is pro-collagen, pro-steroidogenesis and boosts immunity

Manganese (Mn), named after the Greek word for “magic,” is one of 14 essential elements.

Mn is found in all tissues in the body where it is required for normal amino acid, lipid, protein, carbohydrate metabolism and ATP generation. Mn also participates in blood clotting (assisting in keeping the blood the right viscosity), sugar homeostasis (stable blood sugar), immune responsiveness (strong immunity), steroidogenesis, and bone growth (123).

The uptake, utilization and excretion of Mn are tightly regulated and excess Mn is excreted through the bile. (4) Inhalation of manganese leads to toxicity, but toxicity is impossible from natural food sources alone.

Joints, cartilage and collagen

Manganese is totally amazing for repairing, healing and keeping joints/cartilage/collagen optimally healthy.

1) Chondroitin sulfate (of which Mn is a cofactor), together with osteocalcin (requires vitamin D and K2 to be activated), forms the ground substance to which collagen adheres to maintain healthy bone, ligaments and cartilage. (5)

2) Mn is necessary for the synthesis of glycosaminoglycans (GAGs) a.k.a mucopolysaccharides, (67) which provides lubrication and protection for the joints.

3) Mn is the preferred cofactor of enzymes called glycosyltransferases; these enzymes are required for the synthesis of proteoglycans that are needed for the formation of healthy cartilage and bone. (8)

4) Mn is required for the activation of prolidase, an enzyme that functions to provide the amino acid, proline, for collagen formation in human skin cells and joints. (9)

5) Mn is also involved in the cross-linking of collagen fibrils and inhibits elastin-degrading elastases, keeping collagen healthy and strong, as well as keeping the skin supple. (10)

6) Mn is a component of the antioxidant enzyme superoxide dismutase (SOD), which helps fight free radicals and protects the joints from damage during inflammation. Thus it can be used against inflammatory conditions, such as tendonitis, arthritis, lupus, etc. This anti-inflammatory effect is not limited to just the joints of course, but to every part of the body.

If you have inflamed, sore joints, try this trick out from Vince Gironda:

  • 200mg manganese every 3 hours for three days. This will knock that inflammation right out. (very potent)


  • 30mg x3 day for 2 weeks. (more chill)

Best taken with vitamin K2. Supplements at the bottom.

Improves insulin sensitivity

Manganese supplementation significantly increases adiponectin, via an adiponectin-interacting protein called disulfide bond A-like protein. (11) Adiponectin increases insulin sensitivity, reduces inflammation and increases fatty acid oxidation.

Manganese could be great for diabetes by increasing insulin sensitivity and keeping blood glucose stable.

Powerful anti-oxidant

The excess Mn that is not taken up by tissue, or used by enzymatic reactions, is transported to the liver where it binds to bile to be excreted from the body. Lactobacillus (healthy bacteria in the gut) binds to Mn and uses it in order to protect itself, due to MnSODs anti-oxidant effect. Lactobacillus counts on manganese for survival. Lactobacillus probiotics can treat anxiety (as it increases GABA, an inhibitory neurotransmitter), which is a co-morbidity of autism and chronic fatigue syndrome. Reduced gut Lactobacillus leads to the overgrowth of the pathogen, Salmonella. Be sure to consume fermented foods (homemade yogurt from raw milk or beet kvass for e.g.) for your gut bacteria and eat manganese rich foods to ensure their survival.

Manganese rich foods include, macadamia nuts, green leafy vegetables, spice (ginger, cloves, etc)…

Detoxer, anti-ammonia

Mn prevents 1) glutamate and 2) ammonia buildup in the body.

1) Glutamate is an excitatory neurotransmitter, and buildup is neurotoxic and can induce tremor, ataxia, seizures, coma, and even death.

2) Ammonia is a byproduct of protein breakdown. A buildup of ammonia can lead to impaired memory, shortened attention span, sleep-wake cycle disruption, brain edema, intracranial hypertension, seizures, ataxia, and coma and is also neurotoxic.

Glutamine synthase is the enzymes that break down and detoxes glutamate and ammonia to form glutamine, and this enzyme depends on Mn as a cofactor. Inadequate Mn will lead to a buildup of ammonia and glutamate. Thus, this inhibition effect of Mn on glutamate output to the subtantia nigra (SN) results in greater stimulation of dopaminergic neurons. (Verity 1999)

Arginase, the fifth and final enzyme of the urea cycle, is ubiquitous in living systems, and depends upon Mn as a cofactor. This enzyme converts the amino acid arginine to ornithine as well as ammonia to urea. The urea is then released into the bloodstream where it travels to the kidneys and is ultimately excreted in urine.

Mn also helps to prevent and decrease kidney stones, as it is a cofactor in the metabolism/breakdown of oxalates in the liver.

Testosterone & estrogen

Adenylate cyclase (which requires manganese as a cofactor) catalyzes the synthesis of cAMP in the testes. This will increase the transport of cholesterol into the testes and increase steroidogenic enzymes such as StAR and P450scc.

MnSOD also protects the testes and its hormones (testosterone & DHT) against oxidative stress and from being oxidized and destroyed.

Mn stimulates cholesterol synthesis which is then synthesized to bile acid. Bile acid binds to estrogen and other endotoxins. The bile then binds to fiber in the gut and is excreted from the body. Inadequate bile can lead to inadequate estrogen and other endotoxins excretion.

However, beware of just unnecessary supplementation of Mn as high levels of Mn (achieved by supplemental doses) increase estrogen receptors and also prevents the liver from detoxifying estrogen. This leads to an estrogen buildup and greater estrogen sensitivity. (S, Robert, 2015)

Energy production & mitochondrial integrity

Mn is also involved in two enzymes in gluconeogenesis (the production of glucose from non-carbohydrate precursors) namely pyruvate carboxylase (a manganese-containing enzyme), and phosphoenolpyruvate carboxykinase (PEPCK) (a manganese-activated enzyme). This will ensure the body is able to keep blood sugar levels constant during the day. Drops in blood sugar increases stress hormones, such as cortisol, to pick blood sugar back up. Cortisol increases inflammation, the aromatase, degrades testosterone and DHT, prevents detoxification by the liver, suppresses thyroid etc… These problems only come after chronic elevations in cortisol from prolonged periods of stress/malnutrition/under eating etc… It’s very important to eat optimally and stay away from stress. Read more on lowering your cortisol here.

Furthermore, MnSOD protects the mitochondria from oxidative stress, ensuring optimal ATP production.

Extras & supplements

  • Studies show that iron and Mn are inversely correlated, but that by taking Mn doses up to 150mg daily does not reduce someone’s ferritin, and that Mn supplementation can actually fix a mild state of iron deficiency. (s)
  • A zinc deficiency increases Mn uptake in cells significantly which can lead to toxicity.
  • An Mn deficiency might lead to the development of ataxia, a movement disorder characterized by a lack of muscle coordination and balance. This condition is caused by poor development of the otoliths, the structures in the inner ear that are responsible for equilibrium. This could lead to hearing problems and even deafness.
  • Roundup (which is a herbicide) severely depletes manganese and leads to a manganese deficiency in plants, however, it also inhibits liver detoxification and can lead to Mn accumulation in the body and then toxicity. This could then also lead to autism, mitochondrial impairment (1213141516) and with excess glutamate and ammonia in the brain, (171819) could lead to a chronic low-grade encephalopathy (a disease that damages your brain). (2021)
  • Mn binds with very high affinity to phytic acid, an anti-nutrient in food. So eating Mn foods such as grain and nuts, could most likely not fix a deficiency, due to low bio-availability and absorption.


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